Administration of recombinant human granulocyte colony-stimulating factor to normal donors: results of the Spanish National Donor Registry

Abstract

Summary:A Spanish National PBPC Donor Registry has recently been established for short-and long-term safety data collection in normal donors receiving rhG-CSF. To date, 466 donors have been included in the Registry. Median (range) dose and duration of rhG-CSF administration was 10 g/kg/day (4-20) and 5 days (4-8), respectively. Donors underwent a median of two aphereses (range, 1-5). Adverse effects consisted mainly of bone pain (90.2%), headache (16.9%) and fever (6.1%), but no donor discontinued rhG-CSF prematurely due to toxicity. Side-effects were more frequent in donors receiving Ͼ10 g/kg/day than in those with lower doses (82.8% vs 61.8%; P = 0.004). A significant decrease between baseline and post-apheresis platelet counts was the most important analytical finding (229 ؋ 10 9 /l vs 140 ؋ 10 9 /l; P Ͻ 0.0001), with a progressive reduction in platelet count with each apheresis procedure. One donor developed pneumothorax that required hospitalization due to central venous line placement. The mean CD34 ؉ cell dose collected was 6.9 ؋ 10 6 /kg (range, 1.3-36), with only 14 donors (2.9%) not achieving a minimum target of CD34 ؉ cells of 2 ؋ 10 6 /kg. No definitive information about potential long-term side effects is yet available. However, we hope this National Registry will serve as a useful basis for better monitoring of the efficiency and side-effects of cytokine administration in healthy people. Keywords: granulocyte colony-stimulating factor; normal donors; stem cell mobilization; side-effects Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is being widely used to treat neutropenia secondary to chemotherapy and to collect peripheral blood progenitor cells (PBPC) for use in autologous transplantation. [1][2][3] More recently, rhG-CSF has been given to healthy people for granulocyte collection, 4,5 and to mobilize and collect PBPC for allogeneic transplants. [6][7][8][9][10] In the allogeneic setting, the routine use of mobilized PBPC must be based not only on clinical results, but also on the safety of donors. remain important issues. Regarding this, the optimal dose and schedule of rhG-CSF for mobilization of PBPC have not been definitively established, and specific information about short-and long-term biological and clinical effects of rhG-CSF in normal donors is still limited. Thus, a prolonged follow-up of donors is clearly needed in order to rule out the development of toxicity and to ensure that administration of this cytokine to healthy individuals is completely devoid of long-term side-effects. This task will be more easily approached by the development of PBPC national or international donor registries that allow the inclusion of higher number of donors. 11,12 In Spain, a National PBPC Donor Registry has recently been developed to address potential adverse effects of the administration of rhG-CSF to normal donors for PBPC mobilization and collection. The objectives of this registry include a standardized data collection for the different centers administering rhG-CSF to normal d...

G-CSF in Healthy Allogeneic Stem Cell Donors

“…Studies with even higher G-CSF doses [20] indicate that this peak may occur 1 day earlier. On the other hand, there is some evidence that G-CSF doses higher than 10 µg/kg are associated with more frequent side effects [21,22]. Our group used a median dose of 7.5 µg/kg lenograstim (6.8-8.5 µg/kg) during a period of 4.5-5.5 days.…”

Dose and Schedule Effect of G-GSF for Stem Cell Mobilization in Healthy Donors for Allogeneic Transplantation

“…For the patient a high number of transplanted stem cells are important for rapid engraftment, however, adverse effects of G-CSF appeared to be dose dependent [15 -17]. Recently, the Spanish National Donor Registry reported more frequent side effects in donors receiving G-CSF over 10 mg/kg/day compared to those with a dose lower than 10 mg/kg/day (83 vs 62%; p ¼ 0:004) [29].…”

Peripheral Blood Stem Cells for Allogeneic Transplantation: A Review

“…Common minor side effects caused by the administration of growth factors include bone pain, myalgias, headache, and fever, which respond to mild analgesics in over 80% of cases. Longer follow‐up (up to six years) has confirmed the safety of administration of rHuG‐CSF to healthy donors [11, 12].…”